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When calves grow too large in the womb

20.11.2009 - (idw) Forschungsinstitut für die Biologie landwirtschaftlicher Nutztiere

Scientists in Dummerstorf discover candidate gene for fetal growth in mammals

For a long time an increased growth of calves in the womb and associated consequences generated severe problems for breeders and scientists. Furthermore, many studies had proven that prenatal growth of mammals in the womb had significant consequences on life after birth. Now scientists at the Leibniz-Institute for Farm Animal Biology (FBN) in Dummerstorf made a pioneering discovery on the inherited background of divergent fetal growth in the womb in cooperation with colleagues from the Helmholtz-Zentrum Munich, the Technical University Munich, the Kagoshima and the Shirakawa Institute in Japan. They identified a genetic mechanism in cattle that is associated with substantial variation in prenatal growth. Subject of their discovery was a genetic variant in the NCAPG gene on bovine chromosome 6, which should make a major contribution to the divergent development of fetuses in the womb (see background). The key results of the study on the background of fetal growth in cattle are published in the recent November issue of the renowned scientific Journal "Genetics" (abstract: http://www.genetics.org/cgi/content/abstract/183/3/951).

"The variant in the NCAPG gene seems evolutionary rather young, it is however already distributed across many breeds. The function of the gene in mammals has been largely unknown, although it is described to be involved in cell division in lower organism like the fruit fly", pointed out Dr. Christa Kuehn from the Research Unit Molecular Biology of the Leibniz-Institute for Farm Animal Biology .

An increased birth weight frequently results in an impaired delivery or even stillbirth of the calf. This study focussed on the question, which genetic variation is relevant for a high body weight of calves in the womb. For the first time it is possible now to detect a genetic variant via a conventional genetic test, which will enable future targeted selection in cattle to decrease the number of calves with increased birth weight (see background). Thus, the results presented in the study are relevant for both animal welfare and breeding perspectives in cattle production. Furthermore, this study also provides an important contribution to basic research. Frequently, an extreme fetal growth is associated with significant consequences in later life, e.g., increased predisposition to diabetes and obesity in humans.

The Leibniz-Institute for Farm Animal Biology was in charge of major parts of the study including filing the concept, recording of phenotypes and the analysis of the results. The study itself is part of the long-term project SEGFAM dedicated to reveal causative mechanisms for divergent growth and lactation in cattle. The results presented in the current study provide an example, how the mission of the Institute to conduct application-oriented basic science is accomplished. Starting point was a problem relevant to livestock production, the increased birth weight in cattle. While tackling this issue, the elucidation of new, potentially relevant mechanisms for the regulation of fetal growth has contributed to basic research as well.
In the future, research on the NCAPG gene in cattle will focus on two directions. Firstly, the potential of the genetic test in cattle production will be further evaluated. Respective collaborations with breeding organizations are already under way. Secondly, the functional mechanisms of the NCAPG gene in mammals will be elucidated.

Background - conducting the study

In order to establish the specific resource population Charolais sires and German Holstein dams were chosen to form the founder generation (P0). Via artificial insemination and embryo transfer, a first progeny generation (F1), and subsequently by mating F1 individuals, a second progeny generation (F2) were generated. German Holstein females were recipients for both progeny generations. Embryos were collected and transferred at FBN, where also the respective calves were born. After establishing a substantial part of the resource population, an initial scan of ( oder: screen for) regions of the bovine genome relevant for fetal growth was started. From early on, the bovine chromosome 6 was outstanding compared to other parts of the bovine genome. The raw information from the initial scan on the target region on chromosome 6 was refined by fine mapping. Subsequently, the NCAPG was identified as potentially interesting gene by merging information from recent literature, own genetic maps and indication from participating colleagues in Japan and Munich. The NCAPG gene was then systematically investigated for genetic variants. Among the NCAPG variants detected was the mutation that was significantly associated with fetal growth in the womb.

Genetics, Volume 183, Issue 3, November 2009
Table of contents: http://www.genetics.org/content/vol183/issue3/?etoc
For further information: http://www.genetics.org

In 1993 the Leibniz-Institute for Farm Animal Biology based in Dummerstorf near Rostock, was set up in the legal form of a foundation under civil law of the Land Mecklenburg-Vorpommern. The Leibniz Association is a network of 86 scientifically, legally and economically independent research institutes and scientific service facilities. Leibniz Institutes perform strategic and thematically oriented research and offer scientific service of national significance and strive for scientific solutions for major social challenges. Leibniz Institutes contribute to clusters of excellence on fields as Mathematics, Optic Technologies, Materials Research, Medicine, Climate and Environmental Research, Bio- and Nanotechnology as well as humanities, economics and social sciences.

Contact
Leibniz-Institute for Farm Animal Biology
Research Unit Molecular Biology
PD. Dr. Christa Kuehn
Wilhelm-Stahl-Allee 2, 18196 Dummerstorf
T +49 38208 68 70 9
F +49 38208 68 70 2
http://www.fbn-dummerstorf.de/index.php?option=com_content&view=article&id=174&Itemid=842&lang=de


Research Management and Documentation
Dr. Norbert K. Borowy
T +49 38208 68 60 5
F +49 38208 68 60 2
E borowy@fbn-dummerstorf.de
http://www.fbn-dummerstorf.de
http://www.leibniz-gemeinschaft.de

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